Evidence map›Paper›PMID 40317191›Full record

ArticlePlant physiology2025

Characterization of the cyclic dipeptide cyclo(His-Pro) in Arabidopsis.

Romina I Minen, Maria Dolores Camalle, Tyler J Schwertfeger, Fatimah Abdulhakim, Hannah Reish, Leonardo Perez de Souza, Juan C Moreno, Anthony Schilmiller, Venkatesh P Thirumalaikumar, Pallavi Agarwal and 5 more

Abstract read
In one paragraph

Article in Plant physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Romina I MinenBoyce Thompson Institute, Ithaca, NY 14853, USA.
Maria Dolores CamalleMichigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-6299-1124
Tyler J SchwertfegerBoyce Thompson Institute, Ithaca, NY 14853, USA.ORCID 0009-0006-9631-139X
Fatimah AbdulhakimDarwin21 Desert Research Initiative, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.ORCID 0000-0002-8557-0955
Hannah ReishMichigan State University, East Lansing, MI 48824, USA.
Leonardo Perez de SouzaMax-Planck-Institute of Molecular Plant Physiology, Potsdam-Golm 14476, Germany.ORCID 0000-0002-7200-8808
Juan C MorenoDarwin21 Desert Research Initiative, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.ORCID 0000-0001-9722-5262
Anthony SchilmillerMichigan State University, East Lansing, MI 48824, USA.ORCID 0000-0001-7069-7120
Venkatesh P ThirumalaikumarBoyce Thompson Institute, Ithaca, NY 14853, USA.ORCID 0000-0002-5009-1460
Pallavi AgarwalBoyce Thompson Institute, Ithaca, NY 14853, USA.
Caroline F PleckiBoyce Thompson Institute, Ithaca, NY 14853, USA.ORCID 0009-0004-4610-4451
Alisdair R FernieMax-Planck-Institute of Molecular Plant Physiology, Potsdam-Golm 14476, Germany.ORCID 0000-0001-9000-335X
Heribert HirtDarwin21 Desert Research Initiative, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.ORCID 0000-0003-3119-9633
Frank C SchroederBoyce Thompson Institute, Ithaca, NY 14853, USA.ORCID 0000-0002-4420-0237
Aleksandra SkiryczBoyce Thompson Institute, Ithaca, NY 14853, USA.ORCID 0000-0002-7627-7925

Funding

US Department of Agriculture's National Institute of Food and Agriculture RA078000US National Science Foundation 2427055
6 · The paper itself

Abstract

Diketopiperazines (DKPs) are chemically and functionally diverse cyclic dipeptides associated primarily with microbes. Few DKPs have been reported from plants and animals; the best characterized is cyclo(His-Pro), found in the mammalian central nervous system, where it arises from the proteolytic cleavage of a thyrotropin-releasing tripeptide hormone. Herein, we report the identification of cyclo(His-Pro) in Arabidopsis (Arabidopsis thaliana), where its levels increase upon abiotic stress conditions, including high salt, heat, and cold. To screen for potential protein targets, we used isothermal shift assays, which examine changes in protein-melting stability upon ligand binding. Among the identified proteins, we focused on the glycolytic enzyme, cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC1). Binding between the GAPC1 protein and cyclo(His-Pro) was validated using nano-differential scanning fluorimetry and microscale thermophoresis, and we could further demonstrate that cyclo(His-Pro) inhibits GAPC1 activity with an IC50 of ∼200 μm. This inhibition was conserved in human GAPDH. Inhibition of glyceraldehyde-3-phosphate dehydrogenase activity has previously been reported to reroute carbon from glycolysis toward the pentose phosphate pathway. Accordingly, cyclo(His-Pro) supplementation augmented NADPH levels, increasing the NADPH/NADP+ ratio. Phenotypic screening revealed that plants supplemented with cyclo(His-Pro) were more tolerant to high-salt stress, as manifested by higher biomass, which we show is dependent on GAPC1/2. Our work reports the identification and functional characterization of cyclo(His-Pro) as a modulator of glyceraldehyde-3-phosphate dehydrogenase in plants.

Indexed as

ArabidopsisArabidopsis ProteinsDipeptidesPeptides, CyclicGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)Glyceraldehyde-3-Phosphate DehydrogenasesStress, PhysiologicalArabidopsis ProteinsDipeptidesGAPC1 protein, ArabidopsisGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)Glyceraldehyde-3-Phosphate DehydrogenasesPeptides, Cyclic

Identifiers

PMID40317191
PMCPMC12089766

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.